POS0116 EFFICACY AND SAFETY OF VOCLOSPORIN ACROSS PATIENT SUBGROUPS WITH PROTEINURIA ≥2 MG/MG: AN INTEGRATED ANALYSIS OF THE AURA-LV AND AURORA 1 STUDIES
Authors: E. Littlejohn, S. Almaani, V. Birardi, E. Yap, C. Collins
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Proteinuria is the most common manifestation of lupus nephritis (LN) and is a mediator of progressive kidney damage. Early reductions in urine protein creatinine ratio (UPCR) have shown to be predictive of improved long-term outcomes in LN. However, recent studies with monoclonal antibody therapies have demonstrated a lack of efficacy in patients with high proteinuria (UPCR ≥2 to ≥3 mg/mg), potentially due to an increase in renal excretion of drug.<sup>[1]-[4]</sup> In a pooled analysis of the Phase 2 AURA-LV and Phase 3 AURORA 1 studies, the addition of voclosporin to mycophenolate mofetil (MMF) and low-dose steroids resulted in earlier and greater reductions in proteinuria across biopsy classes, races, and ethnicities.<sup>[5]</sup> <h3>Objectives</h3> To further characterize the efficacy and safety of voclosporin in patients with high proteinuria, we have analyzed outcomes in various subpopulations of patients with UPCR ≥2 mg/mg using the pooled dataset. <h3>Methods</h3> Both studies enrolled patients with biopsy-proven LN (Class III, IV, or V ± III/IV) within 6 months (or up to 2 years in AURORA 1) and proteinuria ≥1.5 mg/mg (≥2 mg/mg for Class V). Patients were randomized to voclosporin (23.7 mg BID) or placebo and treated for up to one year (48 weeks [AURA-LV], 52 weeks [AURORA 1]); all patients received MMF and low-dose steroids. For this post-hoc analysis, complete renal response (CRR) rates were evaluated in patients with baseline UPCR ≥2 mg/mg. Complete renal response was defined as UPCR ≤0.5 mg/mg with stable renal function, low-dose steroids, and no rescue medication. Subgroup analyses were based on the following: sex, age, race, ethnicity, biopsy class, and estimated glomerular filtration rate [eGFR] at baseline. Adverse events (AEs) and mean eGFR levels over time were also assessed. <h3>Results</h3> Of the 268 and 266 patients included in the voclosporin and control arms of the pooled analysis, respectively, 217 and 215 patients had a baseline UPCR ≥2 mg/mg (mean [SD], 5.2 [3.4] vs. 4.6 [2.9] mg/mg, respectively). At one year, the change from baseline in least squares (LS) mean (SE) UPCR was -3.8 (0.1) mg/mg in the voclosporin arm compared to -3.1 (0.2) mg/mg in the control arm (difference vs. control, -0.7; p=0.0003). A significantly greater percentage of voclosporin-treated patients achieved CRR at one year compared to the control arm (41.0% vs. 21.9%; odds ratio [OR] 2.48, p&lt;0.0001). CRR rates were numerically greater in voclosporin-treated patients in both sexes and across all ages, races, ethnicities, biopsy classes, and baseline eGFR levels assessed, with OR &gt;1 (Figure 1). Across biopsy classes, the highest rates of CRR were observed in Class III patients treated with voclosporin (50% vs 16.1% in control, p=0.0126), followed by Class IV (44% vs. 23.8%, p=0.0019), Class V with III or IV lesions (37.7% vs. 17% p=0.0306), and Class V (31.3% vs. 28.6%, p=0.81). Similar rates of AEs were reported in both arms, and mean eGFR levels were similar and stable over one year of treatment (Figure 2). <h3>Conclusion</h3> Consistent with results from the overall pooled study population, patients with UPCR ≥2 mg/mg at baseline treated with voclosporin achieved significantly higher renal response rates than patients treated with MMF and low-dose steroids alone regardless of baseline demographics or clinical characteristics. This is clinically relevant given the lack of safe and effective therapies for patients with high proteinuria. <h3>References</h3> [1]Furie RA et al. <i>Ann Rheum Dis. 2022;81:100-107.</i> [2]Jayne D et al. <i>Ann Rheum Dis</i>. 2022;81(4):496-506. [3]Liu T et al. <i>Lupus</i>. Apr 2022;31(4):424-432. [4]Rovin BH et al. <i>Kidney Int</i>. Feb 2022;101(2):403-413. [5]Arriens C et al. Arthritis Care Res. Aug 30 2022. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Emily Littlejohn Speakers bureau: Aurinia Pharmaceuticals Inc., Consultant of: GSK, Salem Almaani Consultant of: Chemocentryx, Aurinia Pharmaceuticals Inc., Kezar, Vanessa Birardi Shareholder of: Aurinia Pharmaceuticals Inc., Employee of: Aurinia Pharmaceuticals Inc., Ernie Yap Shareholder of: Aurinia Pharmaceuticals Inc., Employee of: Aurinia Pharmaceuticals Inc., Chris Collins Shareholder of: Aurinia Pharmaceuticals Inc., Employee of: Aurinia Pharmaceuticals Inc.